The global small-animal/molecular in-vivo imaging market is vast and growing as more pharmaceutical companies and academic institutions realize the scientific and economic benefits of incorporating this approach in disease and drug development research. In the U.S., the preclinical imaging market has transitioned from an emerging market in 2002 to an established one today. American manufacturers presently project the cost of developing a new pharmaceutical to be as high as $300 million for each released drug with an average 12-year development time. In the currently used method of histopathology, a large number of animals are sacrificed to obtain samples for evaluation at different points in time. On the other hand, small animal imaging involves non- invasive imaging techniques that enable molecular targets and genetic processes to be visualized and measured in living laboratory animals. The various imaging modalities (optical, magnetic-resonance, x-ray, nuclear) allow researchers to use the same animal repeatedly thus dramatically reducing overall costs. Small animal imaging manufacturers are unencumbered by the regulatory approval process that is required for clinical diagnostic and therapeutic imaging equipment. This favors rapid commercialization of breakthrough imaging products which should accelerate drug discovery and help make medicinal cures more affordable. We propose to develop a novel computed tomography (CT) system for small-animal imaging. The proposed micro-CT system will use a photon-counting approach to achieve multi-energy imaging capability that will overcome many of the limitations of current dual-energy CT systems. Improvements over those systems will include significantly better energy resolution, more energy levels, flexibility in the selection of the energy ranges, and simultaneous detection of all photon energies in the same detector volume. This last item eliminates problems related to registration of the images that can be a concern in the traditional dual-kVp or dual-detector approaches to dual-energy CT. Our Phase I study demonstrated the feasibility of the proposed small-animal CT detector. During this study we clearly defined our detector concept, tested precursor pixel detector readout devices, prepared preliminary specifications and performed initial design work and circuit simulations. We also reviewed/refined the overall system requirements for small-animal CT with our academic and industrial consultants. Moreover, we investigated various options for detector supply, processing and assembly to ensure Phase II project success and Phase III product viability. During Phase II we plan to develop the components for the CT detector devices and then assemble and characterize their performance under small-animal imaging conditions. The prototype detectors will be evaluated at NOVA and leading academic and industrial laboratories. We likewise plan to develop a prototype small-animal CT system to make larger images (e.g., of phantoms). During Phase III we will seek funding for preclinical trials and pursue commercialization with our industrial collaborators. PUBLIC HEALTH RELEVANCE: Our proposed small-animal CT system would provide both anatomical and functional information within a single imaging modality as enabled by breakthrough multi-energy x-ray detector technology and innovative contrast agents. An important niche application would be that of advanced studies of soft-tissue structures, processes and disease mechanisms based on animal models. These areas of research are growing with the demand for new therapeutic approaches against heart failure, colorectal cancer and osteoarthritis.